THE RELATIONSHIP BETWEEN ENDOTHELIN-1, EVENT-RELATED P300 POTENTIALS,AND PROGNOSIS IN CEREBRAL ARTERIOSCLEROSIS

OBJECTIVES: To search for a potential role of endothelin-l (ET-1), a p otent vasoconstrictor and presumably neurotoxic 21-amino acid peptide, for dysfunction of brain signal processing and cerebrovascular morbid ity in nondemented patients with cerebral arteriosclerosis. DESIGN: Cr oss-sectional study with longitudinal follow-up. SETTING: University-a ffiliated teaching hospital. PARTICIPANTS: A total of 106 nondemented patients with significant stenosis of either the internal carotid (cAD , cases; n = 63, mean age +/- SD, 62 +/- 7 years) or peripheral arteri es (pAD, disease controls; n = 43, 60 +/- 11 years) were investigated before carotid endarterectomy and bypass surgery, respectively. After a mean follow-up of about 19 months, cerebrovascular morbidity of the cAD and pAD patients was evaluated by phone. MEASUREMENTS: Brain signa l processing functions by event-related visual P300 potentials; cerebr ovascular events by a structured telephone interview; the extent of ar teriosclerosis by venous ET-1 concentration. RESULTS: Venous ET-1 leve ls were elevated in both cAD and pAD patient groups, but to the same d egree. In these patients, ET-1 concentration was correlated slightly w ith diastolic blood pressure (r = .334, P = .0326, stepwise regression ). Only in cAD patients with ET-1 levels above the 75th percentile wer e P300 latencies markedly prolonged compared with their lower ET-1 lev el counterparts. Furthermore, the P300 latencies of the cAD patients, but not of the PAD patients, correlated positively with venous ET-1 co ncentration and inversely with pack years of smoking (r = .728, P = .0 002; stepwise regression). In contrast to base-line P300 abnormalities and classical risk factors (e.g., hypertension), high ET-1 levels pre dicted an increased cerebrovascular morbidity of cAD, but not of pAD, patients (P = .0044; Mantel-Cox test). CONCLUSIONS: In nondemented pat ients with cerebral arteriosclerosis, endothelin-l is associated with P300 abnormalities reflecting subclinical dysfunction of brain signal processing. In the long-term, high venous ET-1 levels also appear to p redict a higher cerebrovascular morbidity of cAD patients even after c arotid endarterectomy.